ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1385G>A (p.Arg462His) (rs373650983)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229162 SCV000284544 uncertain significance Neurofibromatosis, type 2 2019-09-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 462 of the NF2 protein (p.Arg462His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs373650983, ExAC 0.03%). This variant has not been reported in the literature in individuals with NF2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001011276 SCV001171577 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-16 criteria provided, single submitter clinical testing The p.R462H variant (also known as c.1385G>A), located in coding exon 13 of the NF2 gene, results from a G to A substitution at nucleotide position 1385. The arginine at codon 462 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001562976 SCV001785834 likely benign not provided 2021-01-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31712784)

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